{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:38:03Z","timestamp":1781534283441,"version":"3.54.5"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Real-world studies on the allergen specific immunotherapy (AIT), omalizumab, and dupilumab associated anaphylactic events are limited. We aimed to analyze the characteristics of drug associated anaphylaxis, and to compare the differences among different drugs.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A disproportionality analysis and Bayesian analysis were used in data mining to identify suspected anaphylaxis associated with AIT, omalizumab, and dupilumab based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2004 to March 2021. Demographic information, time interval to onset, and death rates of AIT, omalizumab, and dupilumab associated anaphylaxis were also analyzed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Totally 9,969 anaphylactic events were identified. Reports of AIT, omalizumab, and dupilumab associated anaphylactic events were 64, 7,784, and 2,121, respectively. AIT had a high reporting odds ratio (ROR) of 5.03 [95%confidental interval (CI) 3.69\u20136.85], followed by omalizumab (ROR 2.24, 95% CI 2.18\u20132.29), and dupilumab had a negative signal for anaphylaxis. In children, most anaphylactic reactions (68%) were reported in the 12\u201317-year-old group. More reports of anaphylaxis related to AIT were in boys (73%), while more reports of anaphylaxis related to omalizumab (63%) and dupilumab (58%) were in girls. Most symptoms occurred on the day of drug initiation. The death rate of AIT related anaphylaxis was the lowest (0%), the death rate of omalizumab was 0.87%, while the death rate of dupilumab was 4.76%. No significant differences were observed among these drugs.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> AIT and omalizumab had a positive signal for anaphylaxis, while dupilumab had a negative signal for anaphylaxis. Patients should be strictly monitored after administration of AIT and also biologics. It also gives us a suggestion for choosing a combined biologics with AIT when the risk of anaphylaxis was considered.<\/jats:p>","DOI":"10.3389\/fphar.2021.767999","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T07:16:29Z","timestamp":1634886989000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Anaphylaxis Associated With Allergen Specific Immunotherapy, Omalizumab, and Dupilumab: A Real World Study Based on the US Food and Drug Administration Adverse Event Reporting System"],"prefix":"10.3389","volume":"12","author":[{"given":"Sainan","family":"Bian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuanggui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1111\/all.14221","article-title":"Efficacy and Safety of Treatment with Biologicals (Benralizumab, Dupilumab, Mepolizumab, Omalizumab and Reslizumab) for Severe Eosinophilic Asthma. A Systematic Review for the EAACI Guidelines - Recommendations on the Use of Biologicals in Severe Asthma","volume":"75","author":"Agache","year":"2020","journal-title":"Allergy"},{"key":"B2","doi-asserted-by":"publisher","first-page":"108","DOI":"10.2500\/aap.2020.41.200001","article-title":"Safety of Allergen Immunotherapy in North America from 2008-2017: Lessons Learned from the ACAAI\/AAAAI National Surveillance Study of Adverse Reactions to Allergen Immunotherapy","volume":"41","author":"Bernstein","year":"2020","journal-title":"Allergy Asthma Proc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.jaci.2004.02.006","article-title":"Twelve-year Survey of Fatal Reactions to Allergen Injections and Skin Testing: 1990-2001","volume":"113","author":"Bernstein","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.jaci.2017.03.050","article-title":"Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines-2016 Revision","volume":"140","author":"Bro\u017cek","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","article-title":"Dupilumab Efficacy and Safety in Moderate-To-Severe Uncontrolled Asthma","volume":"378","author":"Castro","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1080\/14740338.2018.1446940","article-title":"Safety of Humanized Monoclonal Antibodies against IL-5 in Asthma: Focus on Reslizumab","volume":"17","author":"Cazzola","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"B7","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.jaci.2011.04.010","article-title":"American Academy of Allergy, Asthma & Immunology\/American College of Allergy, Asthma & Immunology Omalizumab-Associated Anaphylaxis Joint Task Force Follow-Up Report","volume":"128","author":"Cox","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.jaip.2014.01.004","article-title":"AAAAI\/ACAAI Surveillance Study of Subcutaneous Immunotherapy, Years 2008-2012: an Update on Fatal and Nonfatal Systemic Allergic Reactions","volume":"2","author":"Epstein","year":"2014","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"B9","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.anai.2016.02.001","article-title":"Risk Factors for Fatal and Nonfatal Reactions to Subcutaneous Immunotherapy: National Surveillance Study on Allergen Immunotherapy (2008-2013)","volume":"116","author":"Epstein","year":"2016","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.anai.2021.03.011","article-title":"Risk Factors for Fatal and Nonfatal Reactions to Immunotherapy (2008-2018): Postinjection Monitoring and Severe Asthma","volume":"127","author":"Epstein","year":"2021","journal-title":"Ann. Allergy Asthma ImmunologyAnn Allergy Asthma Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/pds.677","article-title":"Use of Proportional Reporting Ratios (PRRs) for Signal Generation from Spontaneous Adverse Drug Reaction Reports","volume":"10","author":"Evans","year":"2001","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B12","unstructured":"Global Strategy for Asthma Management and Prevention: Global Initiative for Asthma (2020)2020"},{"key":"B13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.anai.2015.04.014","article-title":"Anaphylaxis and Serum Sickness in Patients Receiving Omalizumab: Reviewing the Data in Light of Clinical Experience","volume":"115","author":"Harrison","year":"2015","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1345\/aph.1C515","article-title":"A Brief Primer on Automated Signal Detection","volume":"37","author":"Hauben","year":"2003","journal-title":"Ann. Pharmacother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1517\/14740338.4.5.929","article-title":"The Role of Data Mining in Pharmacovigilance","volume":"4","author":"Hauben","year":"2005","journal-title":"Expert Opin. Drug Saf."},{"key":"B16","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.jaci.2018.02.018","article-title":"Hypersensitivity Reactions to Therapeutic Monoclonal Antibodies: Phenotypes and Endotypes","volume":"142","author":"Isabwe","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e12038","DOI":"10.1002\/clt2.12038","article-title":"Anaphylactic Risk Related to Omalizumab, Benralizumab, Reslizumab, Mepolizumab, and Dupilumab","volume":"11","author":"Li","year":"2021","journal-title":"Clin. Transl Allergy"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1016\/j.jaci.2017.07.013","article-title":"Anaphylaxis Associated with Omalizumab Administration: Risk Factors and Patient Characteristics","volume":"140","author":"Lieberman","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1097\/ACI.0000000000000707","article-title":"Allergen Immunotherapy and Biologics in Respiratory Allergy: Friends or Foes","volume":"21","author":"Malipiero","year":"2021","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1164\/rccm.201810-1944CI","article-title":"Role of Biologics in Asthma","volume":"199","author":"McGregor","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3740","DOI":"10.1002\/sim.2473","article-title":"Extending the Methods Used to Screen the WHO Drug Safety Database towards Analysis of Complex Associations and Improved Accuracy for Rare Events","volume":"25","author":"Nor\u00e9n","year":"2006","journal-title":"Stat. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1002\/pds.2014","article-title":"Selected Control Events and Reporting Odds Ratio in Signal Detection Methodology","volume":"19","author":"Ooba","year":"2010","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B23","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1111\/all.13317","article-title":"EAACI Guidelines on Allergen Immunotherapy: Allergic Rhinoconjunctivitis","volume":"73","author":"Roberts","year":"2018","journal-title":"Allergy"},{"key":"B24","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1111\/all.13264","article-title":"Challenges in the Implementation of the EAACI AIT Guidelines: A Situational Analysis of Current Provision of Allergen Immunotherapy","volume":"73","author":"Ryan","year":"2018","journal-title":"Allergy"},{"key":"B25","doi-asserted-by":"publisher","first-page":"381","DOI":"10.2165\/00002018-200225060-00001","article-title":"Use of Screening Algorithms and Computer Systems to Efficiently Signal higher-Than-expected Combinations of Drugs and Events in the US FDA's Spontaneous Reports Database","volume":"25","author":"Szarfman","year":"2002","journal-title":"Drug Saf."},{"key":"B26","first-page":"227","article-title":"Explaining Odds Ratios","volume":"19","author":"Szumilas","year":"2010","journal-title":"J. Can. Acad. Child. Adolesc. Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A Comparison of Measures of Disproportionality for Signal Detection in Spontaneous Reporting Systems for Adverse Drug Reactions","volume":"11","author":"van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol. Drug Saf."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.767999\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T07:16:33Z","timestamp":1634886993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.767999\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":27,"alternative-id":["10.3389\/fphar.2021.767999"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.767999","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]},"article-number":"767999"}}